{"doi":"10.1093/neuonc/noad086","title":"Long-term safety and efficacy of selumetinib in children with neurofibromatosis type 1 on a phase 1/2 trial for inoperable plexiform neurofibromas","abstract":"BACKGROUND: Selumetinib shrank inoperable symptomatic plexiform neurofibromas (PN) in children with neurofibromatosis type 1 (NF1) and provided clinical benefit for many in our previously published phase 1/2 clinical trials (SPRINT, NCT01362803). At the data cutoff (DCO) of the prior publications, 65% of participants were still receiving treatment. This report presents up to 5 years of additional safety and efficacy data from these studies. METHODS: This manuscript includes data from the phase 1 and phase 2, stratum 1 study which included participants with clinically significant PN-related morbidity. Participants received continuous selumetinib dosing (1 cycle = 28 days). Safety and efficacy data through February 27, 2021 are included. PN response assessed by volumetric magnetic resonance imaging analysis: Confirmed partial response (cPR) ≥20% decrease from baseline on 2 consecutive evaluations. Phase 2 participants completed patient-reported outcome measures assessing tumor pain intensity (Numeric Rating Scale-11) and interference of pain in daily life (pain interference index). RESULTS: For the 74 children (median age 10.3 years; range 3-18.5) enrolled, overall cPR rate was 70% (52/74); median duration of treatment was 57.5 cycles (range 1-100). Responses were generally sustained with 59% (44) lasting ≥ 12 cycles. Tumor pain intensity (n = 19, P = .015) and pain interference (n = 18, P = .0059) showed durable improvement from baseline to 48 cycles. No new safety signals were identified; however, some developed known selumetinib-related adverse events (AEs) for the first time after several years of treatment. CONCLUSIONS: With up to 5 years of additional selumetinib treatment, most children with NF1-related PN had durable tumor shrinkage and sustained improvement in pain beyond that previously reported at 1 year. No new safety signals were identified; however, ongoing monitoring for known selumetinib-related AEs is needed while treatment continues.","journal":"Neuro-Oncology","year":2023,"id":316615,"datarank":2.346476026484602,"base_score":4.584967478670572,"endowment":4.584967478670572,"self_citation_contribution":0.687745121800586,"citation_network_contribution":1.658730904684016,"self_endowment_contribution":0.687745121800586,"citer_contribution":1.658730904684016,"corpus_percentile":null,"corpus_rank":null,"citation_count":97,"citer_count":91,"citers_with_citation_signal":60,"citers_with_endowment":60,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9488,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT01362803"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":109181,"name":"Eva Dombi","orcid":"0000-0002-5323-6995","position":1,"is_corresponding":false},{"id":109180,"name":"Pamela L. 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Fisher","orcid":"0000-0003-3408-3839","position":12,"is_corresponding":false},{"id":109186,"name":"AeRang Kim","orcid":"0000-0002-7813-5568","position":13,"is_corresponding":false},{"id":109187,"name":"Miriam Bornhorst","orcid":"0000-0002-7595-7726","position":14,"is_corresponding":false},{"id":109185,"name":"Brian Weiss","orcid":"0000-0001-5154-3134","position":15,"is_corresponding":false},{"id":80025,"name":"Jaishri O. Blakeley","orcid":"0000-0002-1049-0993","position":16,"is_corresponding":false},{"id":109201,"name":"Malcolm A. Smith","orcid":"0000-0001-9880-9876","position":17,"is_corresponding":false},{"id":109206,"name":"Brigitte C. Widemann","orcid":"0000-0002-9198-7175","position":18,"is_corresponding":false},{"id":109179,"name":"Andrea M. Gross","orcid":"0000-0003-1646-4531","position":0,"is_corresponding":true}],"reference_count":23,"raw_metadata":null,"created_at":"2026-07-19T01:06:44.698773Z","pmid":"37115514","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}